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Background: Stereotactic body radiation therapy (SBRT) is postulated to enhance the recruitment of mesenchymal stem cells (MSCs) into the tumor microenvironment, which promote tumor recurrence. The aim of this study is to determine the molecular mechanisms behind SBRT stimulating MSC migration and differentiation.Methods: In vitro, mediated factors and migrated MSCs (post-SBRT) were generated. In vivo, bone-marrow derived MSCs were identified and harvested from green fluorescent protein (GFP)-expressing transgenic male mice and transplanted into sub-lethally irradiated recipient female mice to establish a model of bone marrow transplantation. Lewis lung carcinoma and malignant melanoma-bearing recipient mice were treated with SBRT, 14 Gy/1 fraction. The migration and differentiation potential of MSCs were characterized.Results: SBRT increased the release of stromal cell derived factor-1α (SDF-1α) and platelet-derived growth factor-B (PDGF-B) by tumor cells; these ligands bound to chemokine (C-X-C motif) receptor 4 (CXCR4) and platelet-derived growth factor receptor-β (PDGFR-β), respectively, on circulating bone marrow-derived MSCs, resulting in engraftment of the MSCs into the tumor parenchyma. The newly-homed MSCs differentiated into pericytes, which induced the tumor vasculogenesis, and promoted tumor regrowth. Targeted therapies, AMD3100 and imatinib abrogated MSC homing, vasculogenesis, and tumor regrowth.Conclusion: Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. MSC migration and maturation may be abrogated with AMD3100 and imatinib. This novel treatment strategy warrants clinical investigation. [ABSTRACT FROM AUTHOR]

Abstract: Background: This retrospective study evaluates the efficacy and safety of surgery and chemotherapy (S +CT) vs. radiotherapy and CT (RT+CT) in patients with limited stage small cell esophageal cancer (LS-SCEC). Patients and methods: Patients included in analysis (from our hospital and the literature) were treated with S+CT or RT+CT between 1989 and 2012. The primary end point was overall survival (OS); secondary end points included tumor response and toxicity. Kaplan–Meier OS curves were compared with the log-rank test. Cox regression analysis was used to determine prognosticators for OS. Results: A total of 127 patients were included: 14 from our hospital and 113 from the literature. Fifty-four (43%) and 73 (57%) patients received S+CT or RT+CT, respectively. The median OS of all patients was 21.0months. OS was longer for those who received RT+CT rather than S+CT (33.0 vs. 17.5months, p =0.02), especially those with N1 disease. Uni- and multi-variate analyses showed tumor location (upper 1/3rd of esophagus) and type of treatment (S+CT) were poor prognostic factors of OS. Conclusion: LS-SCEC patients treated with RT+CT had an improved OS compared to those treated with S+RT. Thus, RT+CT should be considered as a primary approach for these patients. [Copyright &y& Elsevier]